While the Trump administration’s threats to HIV research and services were an inescapable theme at the opening session of the recent Conference on Retroviruses and Opportunistic Infections, participants also heard plenty of science news. The conference, held in San Francisco March 9-12, also featured an accompanying rally in support of science.
Two more stem cell cures
Researchers from Chicago and Oslo, Norway reported that two more people appear to be free of HIV after stem cell transplants for cancer treatment. If the men remain in remission, they will be the ninth and 10th cases of a functional cure after the procedure.
The first such case, former San Francisco resident Timothy Ray Brown (known as the Berlin Patient), received stem cell transplants to treat leukemia from a donor with a rare mutation called CCR5-delta-32 that prevents HIV from entering T cells. Brown stopped antiretroviral treatment, but his viral load did not rebound and researchers could find no evidence of functional HIV anywhere in his body. At the time of his death from leukemia in September 2020, he had been free of HIV for more than 13 years.
Before CROI, seven other cases had been presented at HIV conferences over the years, including three people who appear to be cured after transplants from donors with only one or no copies of the CCR5-delta-32 mutation.
The Chicago Patient is a 67-year-old man who received a stem cell transplant for leukemia from a donor with a double CCR5-delta-32 mutation. This case is notable because the man stopped antiretroviral treatment 15 months after the transplant, experienced viral rebound, restarted antiretrovirals, tried a second treatment interruption two years later, and has now been in HIV remission for 10 months.
This suggests that the resurgent virus came from a residual reservoir of cells infected before the transplant, but the new donor cells with the double mutation “truly were protected,” Dr. Paul Rubinstein of the University of Illinois Chicago Medical Center told reporters. “If virus rebounds, remission is still possible.”
The Oslo Patient is a 58-year-old man who received a stem cell transplant for myelodysplastic syndrome from a brother with the double CCR5-delta-32 mutation – the first known sibling case. He stopped antiretrovirals two years after the transplant, and his viral load remains undetectable and he shows no other signs of HIV two years later.
Stem cell transplantations are too risky for people without advanced cancer, but each new case offers clues that could help scientists develop a more widely accessible functional cure. “Every case is important to build the knowledge about how cure can be achieved,” said Dr. Marius Trøseid of Oslo University Hospital.
Once-yearly PrEP
The highly anticipated approval of twice-yearly lenacapavir PrEP could come as soon as this June, but researchers at Foster City-based Gilead Sciences Inc. are working on once-yearly HIV prevention shots that could have an even bigger impact on the HIV epidemic.
As the Bay Area Reporter reported last year, the PURPOSE 1 trial showed that lenacapavir injections every six months were 100% effective for young cisgender women in Africa – significantly more so than daily Truvada pills (tenofovir disoproxil fumarate/emtricitabine). Findings from PURPOSE 2 showed that lenacapavir injections every six months reduced the risk of HIV acquisition by 96% relative to background incidence and by 89% compared to Truvada for gay and bisexual men and gender-diverse people in the United States and six other countries.
At CROI, Renu Singh, Ph.D., Gilead’s senior director of clinical pharmacology, reported findings from a phase 1 study that enrolled healthy adults with a low likelihood of HIV acquisition. They received a single dose of one of two longer-lasting formulations of lenacapavir administered as intramuscular injections in the buttocks.
Lenacapavir levels were even higher than those of twice-yearly lenacapavir, with plasma levels remaining above the 95% effective concentration for at least 56 weeks with both formulations. The most common side effect was mild injection site pain that was reduced by applying an ice pack before the shots.
Gilead plans to start a phase 3 trial of once-yearly lenacapavir PrEP in the second half of this year, bypassing intermediate phase 2 trials. Data from the trial might be ready for federal Food and Drug Administration review in 2027.
“Once-yearly lenacapavir, if approved, could become an important new HIV prevention option that could help address PrEP adherence and persistence challenges for individuals who need or want PrEP around the world,” Dr. Jared Baeten, Gilead’s senior vice president for clinical development and virology therapeutic area head, stated in a news release.
While these results are potentially groundbreaking, researchers, advocates, and global health officials stress that the promise of long-acting PrEP can only be realized if it is widely available and affordable to everyone who needs it. But access is a growing concern given President Donald Trump’s recent cuts to PEPFAR (the President’s Emergency Plan for AIDS Relief), the main distributor of PrEP worldwide.